The human synovial joints are susceptible to osteoarthritis, rheumatoid arthritis, congenital anomalies, and trauma during war and peacetime, conditions that collectively affect many millions of individuals worldwide. The current clinical gold standards for surgical replacement of the articular condyle of synovial joints such as bone/cartilage grafts and artificial materials suffer from substantial deficiencies such as donor site defects, limited supply, immunorejection, and transmission of pathogens. In response to NIBIB's RFA (EB-03-010), the overall objective of the present proposal is to tissue-engineer human articular condyles of synovial joints using adult mesenchymal stem cells encapsulated in biocompatible polymers. Our long-term goal is to develop tissue-engineered human articular condyles of synovial joints by using patient's own adult stem cells with minimally invasive procedures, and make tissue-engineered condyles ready for operating room use. Our preliminary data demonstrate that human articular condyles were tissue-engineered de novo both in the dorsum of immunodeficient mice using rat stem cells, and in the dorsum of the rabbit using autologous rabbit stem cells, encapsulated in biocompatible polymers. The tissue-engineered articular condyles demonstrated structural characteristics similar to normal articular condyles. Since the adult stem cells were harvested with minimally invasive procedures from the same rabbits for which articular condyles were engineered, the present tissue-engineering approaches present a potential for direct translation into clinical applications. The overall goal of the present proposal is to optimize key parameters of the tissue-engineering process, and to functionalize the tissue-engineered articular condyles. The anticipated findings may have implications in the ultimate ex vivo fabrication of tissue-engineered articular condyles using cell-based regenerative approaches.